This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. SPECIFIC AIMS: This project aims to clarify the neurobiological basis for deficits in response inhibition in laboratory tests of inhibitory control in MA abusers. The objective is to map abnormalities in brain function in MA abusers, as indexed by activations measured by fMRI. PET scans, using [18F]fallypride, will be utilized to assay D2/D3 dopamine receptors in extrastriatal regions of the brain. This project also aims to test a potential medication that has shown promise in improving inhibitory control in human subjects. The knowledge gained may ultimately support evidence-based development of therapeutic interventions targeting this disease symptom in MA dependence, a drug abuse problem that has tremendous global impact. Aim 1. Identify neural substrates of inhibitory control deficits (as indicated by measures of response inhibition and ability to shift set) in MA-dependent subjects. Using data collected from the placebo condition of this study (see Aim 3), we will pair fMRI with performance on a Stop-Signal Task and a Probabilistic Reversal Learning Task in MA-dependent and control subjects.